This grant application describes experiments that are aimed at achieving a detailed understanding of 1) T-cell recognition of antigens and 2) the developmental events that occur in the thymus during T-cell ontogeny. With these goals in mind, we are studying differences in the T-cell receptor (TCR) repertoire that occur between MHC-disparate strains of mice. We are also characterizing the T-cell receptor (TCR) repertoire to a class 2 alloantigen, I-Abm12, and to a class 1 alloantigen, Db. The specific aims of this grant application are stated below. Specific Aim 1: To understand how the number of V beta 5- expressing T-cells is determined in B10 (H-2b) and B10.BR (H-2k) mice. Specific Aim 2: To continue our studies of the T-cell receptor repertoire to the class 2 alloantigen, I-Abm12. Specific Aim 3: To define the amino acid residues critical to the specificity of an alloreactive T-cell receptor using site directed mutagenesis. Specific Aim 4: To determine whether alloreactive T-cells can undergo selection based on their affinity for antigen (i.e. can T- cells undergo affinity maturation?)